Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanis...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856609/ https://www.ncbi.nlm.nih.gov/pubmed/31675181 http://dx.doi.org/10.1002/acn3.50893 |
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author | Magliozzi, Roberta Hametner, Simon Facchiano, Francesco Marastoni, Damiano Rossi, Stefania Castellaro, Marco Poli, Alberto Lattanzi, Federico Visconti, Andrea Nicholas, Richard Reynolds, Richard Monaco, Salvatore Lassmann, Hans Calabrese, Massimiliano |
author_facet | Magliozzi, Roberta Hametner, Simon Facchiano, Francesco Marastoni, Damiano Rossi, Stefania Castellaro, Marco Poli, Alberto Lattanzi, Federico Visconti, Andrea Nicholas, Richard Reynolds, Richard Monaco, Salvatore Lassmann, Hans Calabrese, Massimiliano |
author_sort | Magliozzi, Roberta |
collection | PubMed |
description | OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages. |
format | Online Article Text |
id | pubmed-6856609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68566092019-12-12 Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis Magliozzi, Roberta Hametner, Simon Facchiano, Francesco Marastoni, Damiano Rossi, Stefania Castellaro, Marco Poli, Alberto Lattanzi, Federico Visconti, Andrea Nicholas, Richard Reynolds, Richard Monaco, Salvatore Lassmann, Hans Calabrese, Massimiliano Ann Clin Transl Neurol Research Articles OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages. John Wiley and Sons Inc. 2019-11-01 /pmc/articles/PMC6856609/ /pubmed/31675181 http://dx.doi.org/10.1002/acn3.50893 Text en © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Magliozzi, Roberta Hametner, Simon Facchiano, Francesco Marastoni, Damiano Rossi, Stefania Castellaro, Marco Poli, Alberto Lattanzi, Federico Visconti, Andrea Nicholas, Richard Reynolds, Richard Monaco, Salvatore Lassmann, Hans Calabrese, Massimiliano Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title | Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title_full | Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title_fullStr | Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title_full_unstemmed | Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title_short | Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis |
title_sort | iron homeostasis, complement, and coagulation cascade as csf signature of cortical lesions in early multiple sclerosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856609/ https://www.ncbi.nlm.nih.gov/pubmed/31675181 http://dx.doi.org/10.1002/acn3.50893 |
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